Several inhibitors of HIV have been evaluated in tissue culture systems involving H9 and U937 cells and include inhibitors of phosphorylation, myristylation, polyamine biosynthesis and agents that bind to CD4. A few compounds with anti-HIV activity including 7,8 dioxochlorpromazine and spermidine have been identified and are being evaluated for activity against AZT resistant HIV, in PBMCs and continuous cell lines, singly and in combination with agents currently in clinical use viz. AZT and DDI. Another class of anti-HIV agents we have begun to study are pseudoknot forming oligonucleotides composed of RNA with methyl group modifications. Two oligonucleotides from the RRE region show substantial activity in preliminary experiments based on RT, p24 and quantitative PCR. These studies should enable us to identify 1) appropriate assays for the evaluation of antiviral activity and resistance in vitro and 2) biological and technical issues pertaining to assays used to monitor HIV therapy in vitro, both of which have bearing on the regulatory review of test kits used for this indication.